Group 1 - The Nobel Prize announcement dates for 2025 are set for October 6, 7, and 8, covering the Nobel Prizes in Physiology or Medicine, Physics, and Chemistry [2] - Chinese scientist Chen Zhijian has received multiple prestigious awards, including the Citation Laureate Award, and is considered the closest Chinese scientist to winning a Nobel Prize [2] - Chen Zhijian is recognized for his discovery of how nucleic acids trigger innate immune responses and autoimmune reactions within cells [3] Group 2 - Chen Zhijian was born in 1966 in Fujian Province, China, and graduated with a Bachelor's degree in Biology from Fujian Normal University in 1985 [5] - He obtained his Ph.D. in Biochemistry from the State University of New York at Buffalo in 1991, focusing on the ubiquitin pathway [5] - After his postdoctoral research at the Salk Institute, he worked in various biotech companies, contributing to cancer treatment drug development [5][6] Group 3 - In 1996, Chen collaborated with Harvard's Tom Maniatis to discover that kinases must be "activated" by ubiquitin for the NF-κB signaling pathway to function properly [6] - He established his laboratory at the University of Texas Southwestern Medical Center in 1997, focusing on the role of ubiquitin in immune responses [6] - His research led to significant findings regarding the immune response to RNA viruses and the discovery of key proteins involved in innate immunity [6][8] Group 4 - Chen Zhijian has received numerous awards, including the National Academy of Sciences Molecular Biology Award in 2012 and election to the National Academy of Sciences in 2014 [8] - He was awarded the Breakthrough Prize in Life Sciences in 2019 for elucidating the role of the DNA sensor cGAS in immune responses [11] - In 2023, he received the Horwitz Prize for discovering the cGAS-STING pathway, which is considered a leading indicator for future Nobel Prize winners [12] Group 5 - Chen was awarded the Lasker Basic Medical Research Award in 2024 for his work on the cGAS enzyme and its role in immune and inflammatory responses [15] - The Citation Laureate Award was given to him in 2025 for clarifying the fundamental mechanisms of the cGAS-STING pathway in innate immunity [19] - The awards he has received are indicative of a strong likelihood of future recognition with a Nobel Prize, as many past recipients of these awards have gone on to win the Nobel Prize [12][19]

新生 RNA 的分析对于揭示基因间非编码转录以及理解基因组调控至关重要。在单个细胞中，转录本质上是 随机的——这一特性会影响发育过程中的细胞命运决定。然而，这种转录多样性仍知之甚少，部分原因在 于技术限制。单细胞水平的转录动力学解析对于理解如何通过解读相同的基因组来产生多样化的细胞身份 至关重要。 2025 年 9 月 26 日，清华大学基础医学院 沈晓骅 教授 课题组 （博士生 马绍骞 为第一作者兼共同通讯作 者 ） 在国际顶尖学术期刊 Cell 上发表了题为： Single-cell nascent transcription reveals sparse genome usage and plasticity 的研究论文。 该研究开发了一种 单细胞新生转录组测序 的新方法—— scFLUENT-seq ，能够高灵敏、全基因组地捕获 新生转录本，并更好地保留 RNA 起始信息。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 在高等真核生物中，同一个基因组可分化出成百上千种不同的细胞类型。这种细胞多样性是由转录所驱动 的，转录将基因组信息 （包括编码序列和调控元件） 转化为 RNA 分子，这些 RNA 分子指导蛋 ...

Core Viewpoint - Immunotherapy, particularly immune checkpoint blockade (ICB), presents transformative potential for treating various malignancies, but challenges such as acquired resistance and immune-related adverse events (irAEs) persist, necessitating a dual approach to address both thromboembolic risks and treatment resistance [2][5]. Group 1: Research Findings - A study published in Cell Reports Medicine indicates that the antiplatelet drug Vorapaxar enhances mitochondria-associated ferroptosis, thereby improving cancer immunotherapy outcomes by targeting the FOXO1/HMOX1 axis [3][6]. - Vorapaxar, approved by the FDA in 2014, reversibly inhibits the PAR-1 receptor on platelets, blocking thrombin-mediated platelet activation, which is crucial for antithrombotic therapy [6]. - The study confirms that Vorapaxar binds to FOXO1, inhibiting its phosphorylation and promoting its nuclear translocation, leading to increased expression of heme oxygenase-1 (HMOX1) and subsequent mitochondrial iron overload and ferroptosis [6]. Group 2: Clinical Implications - Vorapaxar has been shown to enhance immune therapy-induced tumor ferroptosis and antitumor immunity in various melanoma mouse models, suggesting its potential as a powerful adjunct in immunotherapy [6][8]. - High co-expression of FOXO1/HMOX1 is associated with improved responses to immunotherapy and prolonged progression-free survival, indicating a promising biomarker for treatment efficacy [6][8]. - Overall, Vorapaxar is positioned as a dual-benefit solution for cancer patients requiring both thrombolytic and immunotherapeutic interventions, addressing the dual challenges of thromboembolism and treatment resistance [8].

Core Viewpoint - The article discusses the development of a biomimetic cilia-based array system inspired by cochlear hair cells, which utilizes acoustic resonance for sound frequency decoding and resonance-responsive drug release [3][4][7]. Group 1: Research Background - The research team, led by Professor Gu Zhen and Researcher Wang Jinqiang from Zhejiang University, published a paper in Nature Biomedical Engineering detailing their innovative approach to sound signal visualization and drug delivery [3][4]. - The human auditory system's ability to perceive sound through the resonance of the basilar membrane and hair cells serves as the foundation for this research [7][8]. Group 2: Technology Development - The team created a micro-scale artificial cilia array (40-200 micrometers) with varying length-to-diameter ratios (30-100) to detect and decode sound frequencies ranging from 100 to 6000 Hz, covering the primary range of human hearing [8]. - The artificial cilia array demonstrated the ability to decode sound signals from piano music and complex human voice signals [8]. Group 3: Drug Delivery Application - The artificial cilia array was tested in a liquid environment, showing that acoustic resonance could significantly enhance the release and diffusion of model drugs [8]. - In diabetes treatment, insulin and glucagon were loaded onto different cilia arrays, allowing for selective drug release triggered by specific acoustic frequencies, effectively regulating blood sugar levels [9]. Group 4: Future Prospects - The artificial cilia array has the potential to be optimized for a broader frequency range and could decode complex acoustic signals, facilitating personalized medical applications [10]. - This technology may enable the detection of various physiological sounds, such as breathing patterns and heartbeats, and could be used for disease monitoring and controlled drug release [10].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 本周 （9 月 22-28 日） ， 西湖大学 作为第一署名单位在 Cell 、 Nature 和 Science 期刊各发表一篇论文，实现了 一周内集齐 CNS 三大顶刊 。这些研究涉及 荧光显微成像 、 无人机 、 mRNA 剪接 领域。 时间分辨荧光蛋白，拓展荧光显微镜应用范围 2025 年 9 月 22 日，西湖大学 张鑫 教授团队 （ 谈自主 、 熊家亨 、 冯嘉辉 为共同第一作者 ） 在国际顶尖学术期刊 Cell 上发表了题为： Time-resolved fluorescent proteins expand fluorescent microscopy in temporal and spectral domains 的研究论文。 该研究首次提出并发展了 时间分辨荧光蛋白 （t ime-resolved fluorescent protein， tr-FP ） 这一变革性工具集， 在时间和光谱域上拓展了荧光显微镜的应用 范围， 为生物学研究提供了整合系统复杂性和定量准确性的全新解决方案。 在这项最新研究中， 张鑫 团队报道了一系列具有理性可调控寿命的时间 ...

Core Viewpoint - Open Science promotes faster and more sustainable scientific development, with Open Access serving as its foundation, providing researchers with increased visibility and collaboration opportunities [2][3]. Group 1: Open Science and Open Access - Open Science is defined as transparent, trustworthy, and accessible science that can be reused and referenced by everyone [2]. - Open Access publishing offers significant benefits, including greater citation advantages, increased usage, and broader impact for research [2]. Group 2: Springer Nature's Open Access Initiatives - Springer Nature offers over 700 pure Open Access journals and more than 2,200 hybrid journals, along with over 3,300 Open Access books, supporting researchers in sharing data and gaining recognition [3]. - The Open Access Content Hub provides resources on Open Science, Open Access journals, books, data, and agreements, allowing users to explore various topics of interest [5][6]. Group 3: Open Access Publishing Options - The Open Access publishing portfolio includes high-impact journals under brands like BMC, Nature Portfolio, Springer, Discover, and Palgrave Macmillan [8]. - Springer Nature has pioneered Open Access book publishing across various fields, including science, technology, medicine, humanities, and social sciences [10]. Group 4: Open Data and Agreements - Springer Nature supports researchers in sharing data and gaining recognition through access to subject repositories, research data courses, and community engagement [13]. - Since 2015, Springer Nature has led the development of transformative agreements, providing Open Access publishing support to researchers from over 3,700 institutions globally [15].

Core Viewpoint - The ketogenic diet (KD) may serve as a potential strategy for treating gliomas by promoting the production of butyrate from gut microbiota, which inhibits glioma progression [4][9]. Group 1: Research Findings - Glioma patients exhibit unique gut microbiota characteristics, specifically a reduction in butyrate-producing bacteria, particularly Roseburia faecis, and lower butyrate levels [6][7]. - KD reshapes the gut microbiota in a mucin-2 dependent manner, enriching Akkermansia muciniphila (AKK) and increasing butyrate production, which activates caspase-3 in microglia, promoting an anti-tumor phenotype [6][7]. - The anti-glioma effects of KD significantly diminish under antibiotic treatment, germ-free conditions, or specific depletion of mucin-2, microglia, or caspase-3 in microglia [6][7]. Group 2: Implications for Treatment - Targeting gut microbiota or supplementing butyrate through KD may represent an effective strategy for glioma treatment [9].

Core Viewpoint - The article discusses the role of the gut microbiome, specifically the bacterium Catenibacterium mitsuokai, in promoting hepatocellular carcinoma (HCC) through mechanisms involving gut barrier disruption and metabolic product secretion [2][3][5]. Group 1: Research Findings - A new carcinogenic gut bacterium, Catenibacterium mitsuokai, has been identified, which promotes the development of HCC by binding to hepatocytes and generating quinolinic acid [3][6]. - Catenibacterium mitsuokai is enriched in the feces and tumors of HCC patients, and it accelerates the carcinogenesis process in both conventional and germ-free mice [5][10]. - The bacterium disrupts the gut barrier and transfers to the liver, where it adheres to HCC cells via the interaction of its surface protein Gtr1/RagA with the γ-catenin receptor on cancer cells [6][10]. Group 2: Mechanistic Insights - The tumor-promoting effect of Catenibacterium mitsuokai is dependent on its secretion of the metabolite quinolinic acid [6][9]. - Quinolinic acid binds to the TIE2 receptor on HCC cells, activating the downstream oncogenic PI3K/AKT pathway, thereby facilitating the progression of liver cancer [6][9].

长期以来，人们一直假设 RNA 聚合酶II （Pol II） 最大亚基 RPB1 的 C 端结构域 （CTD） 能够促进 共转录剪接 ，但 CTD 在招募 Pol II 相关剪接因子方面的必 要性尚未被直接验证。相反，越来越多的证据指向不依赖 CTD 的共转录剪接机制，新近可视化解析的 U1 核内小核糖核蛋白 （snRNP） 与 Pol II 亚基 RPB2 和 RPB12 之间的相互作用即为明证。 该研究始于对另一个 Pol II 亚基 RPB9 在调控性剪接中作用的鉴定，最终揭示了一个前所未有的 U2 辅助因子 （U2AF） 循环机制——该循环划分了共转录剪接 的两个不同阶段。 研究团队首先直接测试了 Pol II CTD 是否为招募多个已明确的 Pol II 相关剪接因子所必需，结果发现，CTD 的截短并不影响这些因子与 Pol II 的结合。与之相 反，研究团队证明了 RPB9 介导 Pol II 与 U2AF1 （负责界定功能性 3' 剪接位点的 U2AF 异源二聚体小亚基） 发生直接相互作用。出乎意料的是，U2AF 异源 二聚体大亚基 U2AF2 并未出现在 Pol II 复合体中。 研究团队进一 ...

Core Insights - The article discusses the rising incidence of cancer globally, with nearly 20 million new cases and 9.7 million cancer-related deaths reported in 2022, highlighting cancer as a leading cause of disease-related mortality [3] - Traditional cancer treatments like chemotherapy and radiotherapy have limitations due to their lack of tumor specificity, leading to significant side effects [3] - Targeted drug delivery strategies, particularly Aptamer-Drug Conjugates (ApDC), are emerging as promising alternatives for cancer treatment, allowing for selective delivery of cytotoxic drugs to tumor cells [3][6] Group 1: Research Development - A recent study published in "Signal Transduction and Targeted Therapy" introduced Sgc8c-M, an ApDC developed by linking a potent anti-mitotic agent MMAE with the PTK7 aptamer Sgc8c, aimed at treating cancers that overexpress PTK7 [4][6] - The study demonstrated the potential of Sgc8c-M through comprehensive evaluations from rodents to non-human primates, indicating its promise as a cancer therapy [4][9] Group 2: Mechanism and Efficacy - Sgc8c-M showed effective tumor regression in various PTK7-overexpressing cancer types, outperforming unlinked MMAE, the chemotherapy drug paclitaxel, and a PTK7-targeted antibody-drug conjugate [6][9] - Pharmacokinetic studies in mice revealed rapid accumulation of the drug in tumors while being quickly cleared from plasma and normal tissues, with over 75% of MMAE excreted within 24 hours [7] Group 3: Safety and Tolerability - Toxicokinetic assessments indicated that Sgc8c-M maintained consistent systemic drug exposure without accumulation after repeated dosing, and high therapeutic doses were found to be safe [7] - Further evaluations in non-human primates showed similar pharmacokinetic characteristics and good tolerability, with no significant accumulation observed after multiple doses [7]